1. Technical Field
This invention concerns sterilization and more particularly devices for testing hydrogen peroxide and related sterilization methods and materials.
2. Background Art
Many methods are used for sterilizing articles, including contacting them for a sufficient time with sterilizing liquids, sterilizing plasma, and/or sterilizing gases (e.g., steam). There obviously need to be methods for determining whether sterilization processes and materials (i.e., devices and other materials) are satisfactory (e.g., do they destroy a sufficient portion of the microorganisms likely to be present).
To help determine whether existing or proposed sterilization processes and devices are functioning or will function satisfactorily, biological indicators (e.g., biological test coupons) have been developed that contain precisely known amounts of specified microorganisms and provide precisely known resistance to sterilization. Chemical indicators have also been developed for the same purpose. Typically, one or more biological indicators are placed in a sterilization device to test (challenge, monitor, validate, etc.) the device and/or a process, the device is operated, and the biological indicators are thereafter removed and assayed to determine whether there was a sufficient reduction in the number of microorganisms. Chemical indicators are used in an analogous manner. Of course, a statistically sufficient sample of each such indicator must be tested to determine whether it is satisfactory for testing the sterilization device/process in question (e.g., is the indicator sensitive enough, does it provide accurate and consistent results).
A device for testing such indicators must be flexible (e.g., be able to be used throughout the ranges of interest for the parameters of interest), be able to rapidly provide uniform conditions throughout the chamber in which the biological or chemical indicators are exposed to (i.e., contacted with) the antimicrobial agent, and be precisely controllable with respect to all parameters (concentration of antimicrobial agent to which the indicator is exposed, exposure time of the indicator to the antimicrobial agent, temperature and pressure at which the exposure occurs, etc.). Such devices are sometimes referred to as “BIER” devices or units (“BIER” signifies “biological indicator evaluator resistometer”), even if they are used for testing chemical indicators.
Use of hydrogen peroxide vapor as the antimicrobial agent is relatively new as compared to use of steam and/or ethylene oxide as the antimicrobial agent. The gas phase containing vaporized hydrogen peroxide sterilant often also contains vaporized water and air. The water is initially present in such gas-phase sterilizing mixtures because hydrogen peroxide is readily commercially available as an aqueous liquid solution and it is more convenient to vaporize the entire solution to provide a hydrogen peroxide-water vapor rather than to try to separate the hydrogen peroxide from the water to obtain a water-free hydrogen peroxide vapor. The air is present in the gas-phase mixtures because it is an inexpensive and readily available gas that can be used as a diluent and/or to adjust the total pressure (a small amount of moisture will also be introduced into the initial gas-phase mixture by the air).
Use of hydrogen peroxide gas-phase sterilizing mixtures presents a number of problems, some of which are unique as compared to the use of older sterilants such as steam and ethylene oxide. For example, hydrogen peroxide immediately starts to decompose as soon as it is vaporized because the stabilizers that help retard or prevent decomposition of the hydrogen peroxide in aqueous solution do not function in the vapor phase (steam and ethylene oxide do not decompose). As a result, hydrogen peroxide vapor must be generated in “real time” (i.e., as it is needed or on demand), particularly for sterilization processes in which the hydrogen peroxide vapor concentration must be maintained above a predetermined minimum. Hydrogen peroxide has a substantially different vapor pressure curve than water (e.g., its normal boiling point is approximately 151° C. as compared to water's normal boiling point of 100° C.). Accordingly, differential evaporation (i.e., distillation) may occur when the aqueous solution of hydrogen peroxide is being vaporized. That makes producing a gas-phase mixture having a constant hydrogen peroxide concentration more difficult and it also increases the need for analytical methods that can rapidly and accurately indicate the hydrogen peroxide concentration (for monitoring and control). The condensation of hydrogen peroxide is influenced by the presence of water, and condensation of the hydrogen peroxide is something that someone operating a vapor-phase hydrogen peroxide sterilization process may wish to avoid. This reinforces the need to be able to carefully control sterilization parameters such as temperature and pressure. All of these factors increase the difficulty and complexity of operating hydrogen peroxide vapor-phase sterilization processes and the difficulty and complexity of adequately and properly testing biological and chemical indicators for such processes.
Documents concerning sterilization, hydrogen peroxide (including detection and determination of hydrogen peroxide and the production of hydrogen peroxide vapor), and related subject matter include U.S. Pat. Nos. Re. 33,007, 2,491,732, 3,851,436, 3,948,601, 4,169,123, 4,169,124, 4,230,663, 4,289,728, 4,296,068, 4,314,344, 4,321,232, 4,366,125, 4,401,755, 4,427,772, 4,437,567, 4,514,361, 4,525,265, 4,528,268, 4,642,165, 4,643,876, 4,671,936, 4,680,163, 4,707,334, 4,717,661, 4,743,537, 4,756,882, 4,795,707, 4,797,255, 4,828,797, 4,839,291, 4,843,867, 4,850,716, 4,863,688, 4,883,641, 4,885,253, 4,909,999, 4,914,034, 4,956,145, 4,992,247, 5,084,239, 5,114,670, 5,115,166, 5,139,957, 5,152,968, 5,167,927, 5,178,829, 5,180,553, 5,184,046, 5,186,893, 5,200,146, 5,244,629, 5,288,460, 5,317,896, 5,325,020, 5,364,590, 5,376,332, 5,413,758, 5,413,759, 5,413,760, 5,439,643, 5,445,792, 5,470,548, 5,472,664, 5,474,908, 5,482,684, 5,486,459, 5,492,672, 5,498,526, 5,503,807, 5,508,009, 5,512,244, 5,516,489, 5,516,648, 5,518,591, 5,525,295, 5,527,508, 5,534,221, 5,556,607, 5,593,649, 5,600,142, 5,603,895, 5,608,156, 5,620,656, 5,645,796, 5,650,693, 5,667,753, 5,674,450, 5,739,004, 5,750,184, 5,753,196, 5,770,393, 5,770,739, 5,779,973, 5,783,146, 5,788,925, 5,789,175, 5,792,435, 5,824,553, 5,830,409, 5,830,683, 5,843,374, 5,847,392, 5,847,393, 5,866,356, 5,870,885, 5,872,004, 5,872,359, 5,876,666, 5,892,229, 5,904,897, 5,911,950, 5,916,816, 5,923,432, 5,928,948, 5,938,917, 5,939,033, 5,942,408, 5,942,754, 5,972,199, 5,980,825, 5,989,852, 6,030,579, 6,036,918, 6,039,922, 6,056,918, 6,071,483, 6,075,246, 6,077,480, 6,094,523, 6,094,887, 6,096,265, 6,120,730, 6,132,680, 6,145,276, 6,149,878, 6,156,267, 6,174,502, 6,183,691, 6,189,368, and 6,203,756; European Patent Document No. EP 1,016,421; British Patent Document Nos. GB 1,582,060 and GB 2,089,213; Patent Cooperation Treaty Publication Nos. WO 00/57927, WO 00/65344, and WO 01/13964; Association for the Advancement of Medical Instrumentation, “Standard for BIER/Steam Vessels” (1981); Association for the Advancement of Medical Instrumentation, “BIER/Steam Vessels” (1992); Association for the Advancement of Medical Instrumentation, “Standard for BIER/EO Gas Vessels” (1982); Association for the Advancement of Medical Instrumentation, “BIER/EO Gas Vessels” (1992); Joslyn Valve Corp., “Biological Indicator Evaluator Resistometer (BIER)—Laboratory Test Systems For Steam And Ethylene Oxide,” 4 pages (undated); U. S. Pharmacopoeia XXII, Official Monograph “Biological Indicators,” pages 1625–1626 (undated); Herzberg, Molecular Spectra and Molecular Structure, II. Infrared and Raman Spectra of Polyatomic Molecules, page 532 (1945); Klapes et al., “Vapor-Phase Hydrogen Peroxide As A Surface Decontaminant And Sterilant,” Applied and Environmental Microbiology, volume 56, number 2, pages 503–506 (1990); Skoog, Holler, Nieman, Principles of Instrumental Analysis (5th edition), pages 311–312 (1998); and Steinfeld, Molecules and Radiation—An Introduction to Modem Molecular Spectroscopy, page 229 (1974). (All of the foregoing documents, as well as all other documents cited or otherwise referenced herein, are incorporated herein in their entireties for all purposes.)
Biological indicators and chemical indicators are known. See, e.g., U.S. Pat. Nos. 4,401,755, 4,514,361, 4,528,268, 4,671,936, 4,717,661, 4,743,537, 4,828,797, 4,839,291, 4,883,641, 4,885,253, 4,914,034, 5,139,957, 5,486,459, 5,498,526, 5,516,648, 5,620,656, 5,739,004, 5,750,184, 5,770,393, 5,789,175, 5,824,553, 5,830,683, 5,866,356, 5,870,885, 5,872,004, 5,916,816, 5,989,852; Patent Cooperation Treaty Publication No. WO 00/65344; and U.S. Pharmacopoeia XXII, Official Monograph “Biological Indicators,” pages 1625-1626 (undated). A “biological indicator” is defined in Association for the Advancement of Medical Instrumentation, “BIER/EO Gas Vessels” (1992), as a “[s]terilization process monitoring device consisting of a standardized, viable population of microorganisms (usually bacterial spores) known to be resistant to the mode of sterilization being monitored.”
Devices for testing biological and/or chemical indicators and/or testing sterilization processes are known. See, e.g., U.S. Pat. Nos. 5,482,684 and 5,942,408; European Patent Document No. EP 1,016,421; Patent Cooperation Treaty Publication No. WO 01/13964; Association for the Advancement of Medical Instrumentation, “Standard for BIER/Steam Vessels” (1981); Association for the Advancement of Medical Instrumentation, “BIER/Steam Vessels” (1992); Association for the Advancement of Medical Instrumentation, “Standard for BIER/EO Gas Vessels” (1982); Association for the Advancement of Medical Instrumentation, “BIER/EO Gas Vessels” (1992); and Joslyn Valve Corp., “Biological Indicator Evaluator Resistometer (BIER)—Laboratory Test Systems For Steam And Ethylene Oxide,” 4 pages (undated).
Association for the Advancement of Medical Instrumentation, “Standard for BIER/Steam Vessels” (1981), includes the following. “This standard establishes requirements for saturated steam vessels intended for the evaluation of the resistance performance of biological indicators (BIs)” (Section 1.1). “The preferred site for monitoring temperature is at the site of placement of the biological indicators” (Section 3.2.4.1). “The time to target temperature (e.g., 121±0.5° C., 204.8 kPa [29.7 psia] shall not exceed 10 seconds” and “[t]he time to exhaust sh be reproducible and shall not exceed 5 seconds” (Sections 3.2.4.2 and 3.2.4.3). “Critical operation of the saturated steam vessel requires that the pressure and temperature of the saturated steam be closely controlled . . .” (Section 4.1.1). “Pressure monitoring devices shall show that vessel pressure within ±3.45 kPa (±0.5 psi) of the saturated steam pressure” (Section 4.2.2). “Temperature control devices shall control the temperature of saturated steam to within ±0.5° C.” (Section 4.3.1). See also Association for the Advancement of Medical Instrumentation, “BIER/Steam Vessels” (1992), a revision of the 1981 version.
Association for the Advancement of Medical Instrumentation, “Standard for BIER/EO Gas Vessels” (1982), includes the following. “This standard establishes requirements for ethylene oxide exposure vessels used to evaluate the resistance performance of biological indicators (BIs) that are intended for use in monitoring ethylene oxide sterilization cycles” (Section 1.1). “The time-to-gas concentration (at test temperatures and percent relative humidity) shall be reproducible at monitored site,” “[t]he time-to-gas concentration for the exposed BI units shall not exceed 60 seconds,” and “[t]he initial time-to-exhaust of the EO [ethylene oxide] from the exposure chamber shall be less than one minute and reproducible (±10 msec [sic]); after the end of the exposure period, items must be removed immediately from the test vessel” (Section 3.2.4). “Temperature control devices shall control the temperature to within ±1° C. at a specific monitored site,” “[e]ach sterilizer shall be operated with a timer that has a precision of ±1.0 second,” “[t]he quantity of gas admitted to the chamber must be controlled to ±5 percent of the gas concentration. . .” (Sections 4.3, 4.4, and 4.5). “There are two types of EO exposure systems. In the first, the test items (BIs) remain outside the exposure chamber until the conditions (temperature, percent relative humidity, and gas concentration) are stabilized; once the system is stable, the test items are exposed to the sterilizing environment by means of an insertion device or equivalent exposure device. In the second, the test items are placed within the exposure chamber; the system is brought to preexposure conditions (temperature and percent relative humidity stabilized); and then the vaporized gas is rapidly admitted into the exposure vessel. In both systems, timing of exposure begins when test units are exposed to the preselected EO conditions.” (Section 5.1.1) See also Association for the Advancement of Medical Instrumentation, “BIER/EO Gas Vessels” (1992), a revision of the 1982 version. In the 1992 version, Section B.2 (entitled “Need For The Standard”) states that “[t]he performance of biological indicators is critical to their acceptance as a means of monitoring ethylene oxide sterilization processes . . .” and that earlier studies “showed that a standard set of test conditions was required to meaningfully evaluate the performance of biological indicator lots.”
U.S. Pat. No. 5,482,684 includes the following. “In addition to utility in monitoring the efficacy of a plasma sterilization cycle, the inventive vessel optionally is adapted to monitor a fluid sterilizing cycle (in addition to plasma), such as a cycle involving a fluid antimicrobial agent. Chemical indicators are useful in indicating such exposure to a fluid antimicrobial agent (or a component or reaction product of the agent), and Example 5 described hereinafter illustrates this aspect of the invention.” (Column 5, lines 29–36) The antimicrobial agent may be hydrogen peroxide (column 6, lines 12–16; column 13, lines 37–45), and the plasma flow is continuous (column 8, lines 29–31). “Sterilizing chamber 14, in a limited sense, is a sterilizer of sorts; however, BIER vessels must perform so that the conditions to which the BIs are subjected are uniform. In addition to uniformity, another important aspect of the inventive BIER vessel is that the BIs being tested are exposed to sterilization conditions that reach a steady state in as short a time as practically possible. For example, in steam BIER vessels, the temperature must rise to the set point within ten seconds of the start of the test, while at the end of the test the steam must be vented away within five seconds. The required rise time in EtO vessels are somewhat slower.” (Column 7, lines 24–35) “Chamber 14 has another outlet 42 whereby a monitor 52 monitors (or determines) the concentration of selected species in a plasma sterilizing cycle downstream of chamber 14. . . . The monitor 52 may include, for example, a mass spectrometer, a photometer, or a filter. The monitor 52 illustrated is a mass spectrometer, which is connected to the interior of a chamber 54, for example, to permit monitoring of the various combination of gases employed in the plasma.” (Column 8, lines 40–53)
Sterilization devices and/or processes utilizing hydrogen peroxide are known (see, e.g., U.S. Pat. Nos. 4,169,123, 4,169,124, 4,230,663, 4,296,068, 4,366,125, 4,437,567, 4,643,876, 4,680,163, 4,707,334, 4,756,882, 4,797,255, 4,863,688, 4,909,999, 4,956,145, 4,992,247, 5,084,239, 5,114,670, 5,152,968, 5,244,629, 5,317,896, 5,413,758, 5,445,792, 5,472,664, 5,482,684, 5,492,672, 5,503,807, 5,508,009, 5,525,295, 5,527,508, 5,556,607, 5,593,649, 5,645,796, 5,667,753, 5,674,450, 5,770,739, 5,779,973, 5,783,146, 5,788,925, 5,792,435, 5,830,409, 5,843,374, 5,847,393, 5,876,666, 5,904,897, 5,911,950, 5,939,033, 5,980,825, 6,030,579, 6,039,922, 6,056,918, 6,077,480, 6,094,887, 6,096,265, 6,120,730, 6,132,680, 6,145,276, 6,149,878, 6,156,267, 6,174,502, 6,183,691, and 6,203,756; British Patent Document Nos. GB 1,582,060 and GB 2,089,213; Klapes et al., “Vapor-Phase Hydrogen Peroxide As A Surface Decontaminant And Sterilant,” Applied and Environmental Microbiology, volume 56, number 2, pages 503–506 (1990)), as are sterilization devices and processes using other modalities (e.g., plasma) with or without hydrogen peroxide (see, e.g., U.S. Pat. Nos. 3,851,436, 3,948,601, 4,321,232, 4,643,876, 4,756,882, 4,850,716, 5,084,239, 5,114,670, 5,115,166, 5,178,829, 5,180,553, 5,184,046, 5,186,893, 5,200,146, 5,244,629, 5,288,460, 5,317,896, 5,325,020, 5,364,590, 5,376,332, 5,413,758, 5,413,759, 5,413,760, 5,439,643, 5,470,548, 5,472,664, 5,512,244, 5,534,221, 5,593,649, 5,603,895, 5,645,796, 5,650,693, 5,753,196, 5,843,374, 5,876,666, 5,923,432, 5,928,948, 6,036,918, 6,071,483, 6,094,523, and 6,149,878; and Patent Cooperation Treaty Publication No. WO 00/57927).
It is known to break liquid hydrogen peroxide (e.g., in an aqueous solution) into particles and use them for, for example, sterilization, and it is known to vaporize liquid hydrogen peroxide (e.g., from such particles) and use the vapor for, for example, sterilization. See, e.g., U.S. Pat. Nos. Re. 33,007, 2,491,732, 4,296,068, 4,366,125, 4,642,165, 4,680,163, 4,707,334, 4,797,255, 4,863,688, 4,909,999, 4,992,247, 5,152,968, 5,525,295, 5,779,973, 6,077,480, and 6,096,265; British Patent Document Nos. GB 1,582,060 and GB 2,089,213; and Klapes et al., “Vapor-Phase Hydrogen Peroxide As A Surface Decontaminant And Sterilant,” Applied and Environmental Microbiology, volume 56, number 2, pages 503–506 (1990).
There are many methods used to detect and/or determine the concentration of an analyte in a mixture or solution. See, for example, U.S. Pat. Nos. 4,314,344, 4,427,772, 4,525,265, 4,795,707, 4,843,867, 5,139,957, 5,167,927, 5,474,908, 5,482,684, 5,516,489, 5,518,591, 5,600,142, 5,608,156, 5,788,925, 5,789,175, 5,847,392, 5,847,393, 5,872,359, 5,892,229, 5,938,917, 5,942,754, 5,972,199, 6,075,246, 6,156,267, and 6,189,368; and European Patent Document No. EP 1,016,421. It is known to detect and/or determine the concentration of a species in gas, vapor, or plasma. See, e.g., U.S. Pat. Nos. 4,314,344, 4,843,867, 5,139,957, 5,167,927, 5,482,684, 5,516,489, 5,600,142, 5,608,156, 5,788,925, 5,789,175, 5,847,392, 5,847,393, 5,872,359, 5,892,229, 6,075,246, 6,156,267, 6,189,368; and European Patent Document No. EP 1,016,421.
It is known to detect the presence of and/or determine the concentration of hydrogen peroxide (see, e.g., U.S. Pat. Nos. 4,427,772, 4,525,265, 4,795,707, 4,843,867, 5,139,957, 5,167,927, 5,474,908, 5,516,489, 5,518,591, 5,600,142, 5,608,156, 5,788,925, 5,789,175, 5,847,392, 5,847,393, 5,872,359, 5,892,229, 5,938,917, 5,942,754, 5,972,199, 6,156,267, and 6,189,368; and European Patent Application No. EP 1,016,421). It is known to detect and/or determine the concentration of hydrogen peroxide using spectrophotometry, e.g., using infrared or near-infrared energy. See, e.g., U.S. Pat. Nos. 5,600,142, 5,847,392, 5,847,393, 5,872,359, 5,892,229, 5,942,754; and European Patent Document No. EP 1,016,421.
Attempts have been made to provide the functionalities required of a BIER unit for processes employing hydrogen peroxide vapor, but none of those attempts has succeeded in providing a device with the required accuracy, reproducibility, flexibility, speed, etc. For example, sealed packages containing articles have been placed in isolators containing hydrogen peroxide vapor and the packages quickly opened to allow hydrogen peroxide vapor to enter the packages to contact the articles; however, the accuracy and reproducibility were not satisfactory, in part because the rate of contact did not even approximate the required rapid commencement of contact, or the required constant hydrogen peroxide concentration throughout the entire contact period at the surface of the articles did not exist, etc.
As far as is known to applicants, there are no devices for accurately, reproducibly, and rapidly testing biological and/or chemical indicators for hydrogen peroxide sterilization (and as far as applicants know, there are no standards that anyone contemplating designing such a device could use). Thus, there is a need for such devices. Separate and apart from that, there is a need for devices that are sufficiently flexible, able to rapidly provide uniform conditions, precisely controllable, etc. for testing (including conducting research and development activities) processes and materials (i.e., devices and other materials) in the sterilization field involving hydrogen peroxide.